The normal small intestinal mucosa is composed of the mucosal epithelium, lamina propria and muscularis mucosa. The mucosal epithelium is the mucosal surface, consisting of a single-layer columnar epithelial lining. It along with the lamina propria forms a finger-like projection called intestinal villus, and the epithelium of the roots of villus sinking into the lamina propria forms crypt. Original epithelial cells proliferate in the crypts and shift to the top of villus, and in the process transit to physiological maturity. Generally, epithelial cells up to the middle of villus are fully in function. The renewal of the small intestinal villus occurs when the old epithelial cells at the top of villus constantly fall off to the intestinal lumen, and the proliferative cells move up to the top. The small intestinal epithelium has a high turnover rate. Normal replacement of the whole mucosa takes 5-6 days in humans, indicating that the epithelium of the small intestine loses 2-5×107 cells in every minute.
When the intestinal mucosa is injured, the epithelial cells of intestinal mucosa begin to shrink, denature and shed, and the cell renewal slows down. Currently, the major protective measure on the intestinal mucosal injury is enteral nutrition, which provides the intestinal mucosal immune cells with adequate nutrition matrix through the nutrient solution. In recent years, immune-enhancing enteral nutrition with special nutrients such as glutamine and arginine is increasingly used in clinic. And these substances can stimulate the mucosal immune response, mediate cytokine production and release, reduce excessive inflammation response and promote mucosal repair (Li, Y., Z. Yu, F. Liu, et al. Tumori 2006(92):396-401; Barasch, A., D. E. Peterson. Oral Oncol 2003(39):91-100; Goncharova, G. I., V. G. Dorofeichuk, A. Z. Smolianskaia, et al. Antibiot Khimioter 1998(34):462-466). In addition, the bifidobacterium and Chinese herbal medicine are used in clinic to reduce chemotherapy-induced intestinal mucosal injury (Boerma, M., J. Wang, A. F. Burnett, et al. Cancer Res 2007(67):9501-9506). Cytokines and chemokines secreted by small intestinal mucosal epithelial cells play an important role in the stability of the small intestine function. More and more studies have focused on the application of these factors in chemotherapy-induced intestinal mucosal damage and repair. IL-11 significantly reduces the mice mucosal damage induced by radiotherapy and chemotherapy, and plays different effects on the mucosal cells before and after injury, thus protects the mucosa by reducing damage and promoting repair after injury (Gibson, R. J., D. M. Keefe, F. M. Thompson, et al. Dig Dis Sci 2002(47):2751-2757; Naugler, K. M., K. A. Baer, and M. J. Ropeleski. 2008 Am J Physiol Gastrointest Liver Physiol). Latest research results indicate that it plays effect through the MEK pathway (Kim, K. A., M. Kakitani, J. Zhao, et al. Science 2005(309):1256-1259). In 2005, Klm et al. found that human growth factor R-spondin 1 significantly promotes the proliferation of crypt epithelial cells leading to the coarsening and extending of the small intestine and large intestine, and reduces the cell damage, the incidence of diarrhea and weight loss caused by chemotherapeutic agent 5-fluorouracil (Kim, K. A., J. Zhao, et al. Cell Cycle 2006(5):23-26; Booth, D., J. D. Haley, A. M. Bruskin, et al. Int J Cancer 2005(86):53-59). TGF-133 inhibits the cell cycle of epithelial cells in the G0 or G1 phase to protect small intestine from chemotherapy (Farrell, C. L., J. V. Bready, K. L. Rex, et al. Cancer Res 1998(58):933-939). KGF is another factor that can promote proliferation and has chemoprotective effect on mucosal epithelial cells. And KGF used before chemotherapy can greatly improve the survival ratio of crypt cells (Gibson, R. J., J. M. Bowen, and D. M. Keefe. et al. Int J Cancer 2005(116):464-470; Dinarello. Blood 1996(87):2095-2147). However, the safety of these growth factors has not yet been completely confirmed. Thus some scholars believe that the growth factors could promote the growth of tumor cells with growth factor receptors, and therefore the application of these drugs is limited.